A survey of patient informational preferences when choosing between medical and surgical therapy for ulcerative colitis: a sub-study from the DISCUSS project.

AIM: People living with ulcerative colitis (UC) have two broad treatment avenues, namely medical or surgical therapy. The choice between these can depend on patient preference as well as the receipt of relevant information. The aim of this study was to define the informational needs of patients with UC. METHOD: A postal survey was designed to capture respondent demographics, treatment experienced within the previous 12 months and informational preferences by rating a long list of items. It was delivered through two hospitals that provide tertiary inflammatory bowel disease services. Descriptive analyses were performed to describe demographics and experiences. Principal component analysis was carried out using a varimax rotation to investigate informational needs. RESULTS: A total of 101 responses were returned (20.1% response rate). The median age of respondents was 45 years and the median time since diagnosis was 10 years. Control preferences skewed towards shared (42.6%) or patient-led but clinician-informed (35.6%). Decision regret was low for the population (median 12.5/100, range 0-100). Key informational needs related to medical therapy were benefits and risks of long-term therapy, burden of hospital attendance, reproductive health, need for steroid treatment and impact on personal life. For surgery, these were stoma information, effect on daily life, effect on sexual and reproductive health, risks and benefits and disruption of life due to surgery. CONCLUSION: This study has identified key areas for discussion when counselling patients about treatment decisions around medical therapy and surgery for UC.

Testing for causality between systematically identified risk factors and glioma: a Mendelian randomization study.

BACKGROUND: Whilst epidemiological studies have provided evidence of associations between certain risk factors and glioma onset, inferring causality has proven challenging. Using Mendelian randomization (MR), we assessed whether associations of 36 reported glioma risk factors showed evidence of a causal relationship. METHODS: We performed a systematic search of MEDLINE from inception to October 2018 to identify candidate risk factors and conducted a meta-analysis of two glioma genome-wide association studies (5739 cases and 5501 controls) to form our exposure and outcome datasets. MR analyses were performed using genetic variants to proxy for candidate risk factors. We investigated whether risk factors differed by subtype diagnosis (either glioblastoma (n = 3112) or non-glioblastoma (n = 2411)). MR estimates for each risk factor were determined using multiplicative random effects inverse-variance weighting (IVW). Sensitivity analyses investigated potential pleiotropy using MR-Egger regression, the weighted median estimator, and the mode-based estimator. To increase power, trait-specific polygenic risk scores were used to test the association of a genetically predicated increase in each risk factor with glioma onset. RESULTS: Our systematic search identified 36 risk factors that could be proxied using genetic variants. Using MR, we found evidence that four genetically predicted traits increased risk of glioma, glioblastoma or non-glioblastoma: longer leukocyte telomere length, liability to allergic disease, increased alcohol consumption and liability to childhood extreme obesity (> 3 standard deviations from the mean). Two traits decreased risk of non-glioblastoma cancers: increased low-density lipoprotein cholesterol (LDLc) and triglyceride levels. Our findings were similar across sensitivity analyses that made allowance for pleiotropy (genetic confounding). CONCLUSIONS: Our comprehensive investigation provides evidence of a causal link between both genetically predicted leukocyte telomere length, allergic disease, alcohol consumption, childhood extreme obesity, and LDLc and triglyceride levels, and glioma. The findings from our study warrant further research to uncover mechanisms that implicate these traits in glioma onset.

Exploring factors associated with the uneven utilization of telemedicine in Norway: a mixed methods study.

BACKGROUND: Norway has a long history of using telemedicine, especially for geographical reasons. Despite the availability of promising telemedicine applications and the implementation of national initiatives and policies, the sustainability and scaling-up of telemedicine in the health system is still far from accomplished. The main objective of this study was to explore and identify the multi-level (micro, meso and macro) factors affecting telemedicine utilization in Norway. METHODS: We used a mixed methods approach. Data from a national registry were collected to analyze the use of outpatient visits and telemedicine contacts in Norway from 2009 to 2015. Interviews with key stakeholders at national, regional and local level helped complete and contextualize the data analysis and explore the main issues affecting the use of telemedicine by health authorities and hospitals. Relevant national documents were also used to support, contradict, contextualize or clarify information and data. RESULTS: Telemedicine use in Norway from 2009 to 2015 remained very low, not exceeding 0.5% of total outpatient activity at regional level and 0.1% at national level. All four regions used telemedicine. Of the 29 hospitals, 24 used it at least once over the 7-year period. Telemedicine was not used regularly everywhere, with some hospitals using it sporadically. Telemedicine was mostly used in selected specialties, including rehabilitation, neurosurgery, skin and venereal diseases. Three major themes affecting implementation and utilization of telemedicine in Norway emerged: (i) governance and strategy; (ii) organizational and professional dimensions; (iii) economic and financial dimensions. For each theme, a number of factors and challenges faced at different health care levels were identified. CONCLUSIONS: This study allowed shedding light on multi-level and interdependent factors affecting utilization of telemedicine in Norway. The identification of the main implementation and utilization challenges might support decision makers and practitioners in the successful scaling-up of telemedicine. This work provides a knowledge base useful to other countries which intend to implement telemedicine or other digital health services into their healthcare systems.

An exploration into the causal relationships between educational attainment, intelligence, and wellbeing: an observational and two-sample Mendelian randomisation study.

Educational attainment is associated with a range of positive outcomes, yet its impact on wellbeing is unclear, and complicated by high correlations with intelligence. We use genetic and observational data to investigate for the first time, whether educational attainment and intelligence are causally and independently related to wellbeing. Results from our multivariable Mendelian randomisation demonstrated a positive causal impact of a genetic predisposition to higher educational attainment on wellbeing that remained after accounting for intelligence, and a negative impact of intelligence that was independent of educational attainment. Observational analyses suggested that these associations may be subject to sex differences, with benefits to wellbeing greater for females who attend higher education compared to males. For intelligence, males scoring more highly on measures related to happiness were those with lower intelligence. Our findings demonstrate a unique benefit for wellbeing of staying in school, over and above improving cognitive abilities, with benefits likely to be greater for females compared to males.

Calcium and salinity as selective factors in plate morph evolution of the three-spined stickleback (Gasterosteus aculeatus).

Identifying the causal factors underlying natural selection remains a key challenge in evolutionary biology. Although the genetic basis for the plate morph evolution of three-spined stickleback (Gasterosteus aculeatus) is well described, the environmental variables that form the basis for different morphs are not understood. We measured the effects of dissolved calcium and salinity on the growth of sticklebacks with different plate morphs from Scotland and Poland. There was a significant interaction of calcium with plate morph for fish from both regions, with complete morph sticklebacks growing more slowly at low calcium concentrations and low morph sticklebacks showing divergent responses to calcium concentration. A Scottish anadromous population showed evidence of local adaptation to high salinity, which was independent of plate morph. Polish and Scottish populations diverged in their response to salinity, suggesting a difference in osmotic regulation. The results implicate a role for calcium in selecting for plate morph evolution in sticklebacks, possibly as a limiting element in skeletal growth.

Community photo-triage for skin cancer referrals: an aid to service delivery.

BACKGROUND: We wished to investigate the potential for extending the capacity of the specialist service by using community-based photo-triage for suspected skin cancers. AIMS: To compare the outcomes and costs of conventional and photo-triage referral pathways. METHODS: This was an observational study of conventional and photo-triage referrals. Patients referred for initial photo-triage were invited to visit a medical photographer located in community health centres, who would take high-quality close-up and dermatoscopic images of the patients' lesions. A dermatologist then reviewed the images, and triaged patients to specific treatment clinics. All patients referred by conventional letter were offered initial appointments at the consultant-delivered skin cancer clinic. The difference in costs was assessed by modelling health service use under both pathways. RESULTS: Photo-triage permitted 91% of patients (263/289) to achieve definitive care at first visit to the specialist team, compared with only 63% (117/186) via the conventional referral pathway. The mean waiting time to definitive treatment for patients with skin cancer was slightly reduced with photo-triage. Photo-triage permitted direct booking for 45% of patients to attend a nurse-delivered clinic, 22% to attend directly for surgery, 2% to attend a community general practice clinic and 2% to be referred on electronically to another specialty. This reduced by 72% the number of patients requiring attendance to the consultant clinic, freeing up capacity. Despite the cost of providing medical photography, there was a small cost saving of around £ 1.70 per patient using photo-triage. CONCLUSIONS: Community photo-triage improved referral management of patients with suspected skin cancer, improving the delivery of definitive care at first visit and achieved an increased service capacity. Cost comparison found that the photo-triage model described was marginally cheaper than conventional care, and reduced hospital visits. An integrated primary-secondary care referral pathway that includes photo-triage facilitates a more efficient specialist service while ensuring that all suspicious lesions are viewed by an experienced dermatologist.

Using videotelephony to support paediatric oncology-related palliative care in the home: from abandoned RCT to acceptability study.

Videotelephony (real-time audio-visual communication) has been used successfully in adult palliative home care. This paper describes two attempts to complete an RCT (both of which were abandoned following difficulties with family recruitment), designed to investigate the use of videotelephony with families receiving palliative care from a tertiary paediatric oncology service in Brisbane, Australia. To investigate whether providing videotelephone-based support was acceptable to these families, a 12-month non-randomised acceptability trial was completed. Seventeen palliative care families were offered access to a videotelephone support service in addition to the 24 hours 'on-call' service already offered. A 92% participation rate in this study provided some reassurance that the use of videotelephones themselves was not a factor in poor RCT participation rates. The next phase of research is to investigate the integration of videotelephone-based support from the time of diagnosis, through outpatient care and support, and for palliative care rather than for palliative care in isolation. Trial registration ACTRN 12606000311550.

The Darwinian stickleback Gasterosteus aculeatus: a history of evolutionary studies.

The history of studies on the taxonomy and evolutionary biology of the three-spined stickleback Gasterosteus aculeatus from the 18th century to the present is reviewed. After the publication of Darwin's Origin of the Species, four important dates, 1925, 1947, 1967 and 2001, are identified as marking major gains in the understanding of the evolution of the diversity in morphological, life-history, physiological and behavioural traits that characterizes G. aculeatus. The period 1925-1970 led to the identification of the main themes of research: status and adaptive significance of lateral-plate morphs; inter and intrapopulation trait variation in freshwater resident G. aculeatus and the adaptive significance of the variation. Between 1970 and 2001, these themes were investigated using variation observed particularly along the Pacific coast of the U.S.A. and Canada, notably in the Cook Inlet region of Alaska and the Haida Gwaii Archipelago. Studies on adaptive radiation and reproductive isolation in lacustrine, ecomorph pairs (limnetics and benthics) discovered in the Strait of Georgia region have been particularly productive. From 2001, the application of genomic studies to these problems began to open up the study of the relationships between genotype, phenotype and selective advantage to causal analysis.

Effect of spawning number and ration on reproductive performance of the batch-spawning three-spined stickleback Gasterosteus aculeatus.

An experiment quantified the effect of food ration and spawning number on the breeding season reproductive performance of batch-spawning, female three-spined sticklebacks Gasterosteus aculeatus. Individually housed females were maintained on fixed rations of 2, 4, 8 or 16% of their initial postspawning mass of live enchytraeid worms from immediately after their first spawning until they ceased spawning. Number of spawnings correlated positively with ration. Total breeding season reproductive investment (total wet mass of eggs produced as a percentage of initial postspawning female mass) ranged from 38% at the 2% ration to 147% at the 16% ration. At the lower rations, postspawning mass, batch fecundity and wet and dry masses of the batch declined over successive spawnings, with the rate of decline inversely related to ration. At the highest ration, there was no decline in batch fecundity and postspawning mass increased over successive spawnings. Mean reproductive investment per inter-spawning interval was higher at the highest ration, but at all rations declined over successive spawnings. Mean reproductive effort per inter-spawning interval (wet mass of eggs spawned as a percentage of the wet mass of food consumed over the inter-spawning interval) was inversely related to ration. At the higher rations, reproductive effort showed no trend over successive spawnings. Neither spawning number nor ration had a systematic effect on egg diameter, wet mass per egg, dry mass per egg or total lipid content of the eggs. If the rate of food intake was insufficient, although batch fecundity declined, the main adjustment was a reduction in the number of spawnings in the breeding season.

Health staff priorities for the future development of telehealth in Western Australia.

INTRODUCTION: The views of health managers and physicians working in non-metropolitan areas of Western Australia (WA) were sought about which telehealth services are most needed. METHOD: Chief executives and nurse managers of rural hospitals were sent a simple, open-ended questionnaire and asked to consider the current health situation and problems in their area, and to list the four most-needed telehealth services. In addition, they were asked to hand the questionnaire to one of the GPs or medical officers working with them. A total of 78 questionnaires were sent. RESULTS: The response rate for managers and doctors was 51% and 43%, respectively. The first priority of the managers was wound care (28%). The first priority of the doctors was psychiatry (35%). The collective priorities of the two groups were similar, with managers listing wound care, emergency, psychiatry and ophthalmology; and doctors listing psychiatry, wound care, emergency and ophthalmology. CONCLUSION: Prioritizing potential telemedicine applications is a subject largely absent from the literature. When planning future telehealth applications, the opinion of local health staff who understand the requirements of patients in their region will assist in identifying real needs and lead to the provision of better health services for rural patients.

Metabolic studies of radioiodinated serum amyloid P component in normal subjects and patients with systemic amyloidosis.

125I-Serum amyloid P component (SAP), injected intravenously into 10 normal subjects, remained predominantly intravascular with mean (SD) T1/2 (half time) in plasma of 24.5 (5.9) h. The fractional catabolic rate of 68 (19)% of the plasma pool per day was more rapid than other reported human plasma proteins. All radioactivity was excreted in the urine by 14 d. In 16 patients with monoclonal gammopathy or chronic inflammatory diseases, but without amyloidosis, 125I-SAP metabolism was normal. However, among 45 patients with biopsy-proven systemic amyloidosis (25, amyloid A type; 20, amyloid L type), 125I-SAP was cleared from the plasma more rapidly, accumulated in the amyloid deposits, and persisted there. The T1/2 in amyloid, measured directly with 131I-SAP, was 24 d. Repeat studies after 6-18 mo were notably consistent in normals but changed significantly in amyloid patients, generally correlating with clinical signs of disease progression. Measurements of 125I-SAP turnover may thus be of value for diagnosis and monitoring of amyloidosis. Analysis of SAP metabolism in amyloidosis suggests that plasma SAP is in dynamic equilibrium with a very large amyloid pool, and in two autopsies the total mass of SAP in the amyloid deposits was 2,100 and 21,000 mg, respectively.

Detailed optical study of the transparent wing membranes of the dragonfly Aeshna cyanea.

The optical properties of transparent single membranes on the wings of the dragonfly Aeshna cyanea have been investigated. These membranes comprise one central thick cuticular layer covered dorsally and ventrally with typical odonatan wax pruinosity. Optical characterisation of individual membranes reveals they can support optical guided modes comprising differential polarisation reflection. We suggest this may offer an intraspecific signalling channel. The guided modes' characteristics depend on membrane thickness and the nature of the wax pruinosity. We accurately modelled multiple optical data sets simultaneously, thereby inaugurally quantifying the roughness of the pruinosity and the complex refractive indices of the wax and the odonatan cuticle.

Quantification of the magnification and distortion effects of a pediatric flexible video-bronchoscope.

BACKGROUND: Flexible video bronchoscopes, in particular the Olympus BF Type 3C160, are commonly used in pediatric respiratory medicine. There is no data on the magnification and distortion effects of these bronchoscopes yet important clinical decisions are made from the images. The aim of this study was to systematically describe the magnification and distortion of flexible bronchoscope images taken at various distances from the object. METHODS: Using images of known objects and processing these by digital video and computer programs both magnification and distortion scales were derived. RESULTS: Magnification changes as a linear function between 100 mm (x1) and 10 mm (x9.55) and then as an exponential function between 10 mm and 3 mm (x40) from the object. Magnification depends on the axis of orientation of the object to the optic axis or geometrical axis of the bronchoscope. Magnification also varies across the field of view with the central magnification being 39% greater than at the periphery of the field of view at 15 mm from the object. However, in the paediatric situation the diameter of the orifices is usually less than 10 mm and thus this limits the exposure to these peripheral limits of magnification reduction. Intraclass correlations for measurements and repeatability studies between instruments are very high, r = 0.96. Distortion occurs as both barrel and geometric types but both types are heterogeneous across the field of view. Distortion of geometric type ranges up to 30% at 3 mm from the object but may be as low as 5% depending on the position of the object in relation to the optic axis. CONCLUSION: We conclude that the optimal working distance range is between 40 and 10 mm from the object. However the clinician should be cognisant of both variations in magnification and distortion in clinical judgements.

Referral patterns in a global store-and-forward telemedicine system.

We examined the nature of the referral patterns in the email telemedicine network operated by the Swinfen Charitable Trust with a view to informing long-term resource planning. Over the first six years of operation, 62 hospitals from 19 countries registered with the Trust in order to be able to refer cases for specialist advice; 55 of these hospitals (89%) actually referred cases during this period. During the first six years of operation, nearly 1,000 referrals were submitted and answered, from a wide range of specialty areas. Between July 2002 and March 2005 the referral rate rose from 127 to 318 cases per year. The median length of time required to provide a specialist's response was 2.3 days during the first 12 months and 1.8 days during the last 12 months. Five hospitals submitted cases for more than four years (together sending a total of 493 cases). Their activity data showed a trend to declining referral rates over the four-year period, which may represent successful knowledge transfer. There is some evidence that over the last three years the growth in demand has been exponential, while the growth in resources available (i.e. specialists) has been linear, a situation which cannot continue for very long before demand outstrips supply.

Skeletal blood flow, iliac histomorphometry, and strontium kinetics in osteoporosis: a relationship between blood flow and corrected apposition rate.

In 20 untreated patients with idiopathic or postmenopausal osteoporosis, kinetic studies of skeletal blood flow (using 18F) and bone turnover (using 85Sr) were combined with dynamic histomorphometry performed on transiliac biopsies taken within 6 weeks of each other. In 8 patients the combined studies were repeated after treatment. A further 5 patients were studied only while receiving treatment. As expected, skeletal blood flow measured by 18F correlated with an index of 85Sr uptake into the exchangeable pools of bone. Additionally and independently, skeletal blood flow correlated with an index of the work rate of the osteoblasts in each multicellular unit of bone (the corrected apposition rate of Parfitt). These correlations were statistically significant in both the untreated patients (P less than 0.05) and the whole group (P less than 0.001). Further indices related to bone turnover at the level of the skeleton as a whole were significantly associated with skeletal blood flow only in the combined group.

Inhibition of dihydropyrimidine dehydrogenase by 5-propynyluracil, a metabolite of the anti-varicella zoster virus agent netivudine.

OBJECTIVE: To study the effects of the anti-herpetic drug netivudine on dihydropyrimidine dehydrogenase activity in elderly volunteers and to relate them to concentrations of netivudine and its metabolite 5-propynyluracil. METHODS: Three groups of eight elderly volunteers received 400 or 800 mg netivudine or placebo once daily for 8 days. Plasma netivudine, 5-propynyluracil, and uracil, an indirect measure of dihydropyrimidine dehydrogenase activity, were assayed before the first dose and on days 2, 3, 5, 7 and 8. Full plasma profiles of netivudine and 5-propynyluracil were determined after the last dose. RESULTS: Plasma uracil was unquantifiable in all subjects before the first dose and at all time points in the placebo group. In recipients of netivudine it reached a plateau between days 3 and 5, with mean values of 23.2 and 23.5 mumol/L on day 8 in the subjects who received 400 and 800 mg. Plasma netivudine concentrations were approximately dose proportional, but 5-propynyluracil concentrations were similar in both groups. The half-maximal rise in plasma uracil occurred after a cumulative 5-propynyluracil exposure of 120 mumol/L.hr; such exposures will be achieved even after doses as low as 50 to 100 mg daily. CONCLUSIONS: Netivudine dosing produces complete inhibition of plasma dihydropyrimidine dehydrogenase. Coadministration with the antimetabolite 5-fluorouracil will require a substantial reduction in 5-fluorouracil dose to avoid toxicity but may also improve the therapeutic index of 5-fluorouracil.

Analysis of the effect of bezafibrate on the oxygen dissociation curve of human hemoglobin.

Analysis of the effects of a range of concentrations of the antihyperlipoproteinemia drug, bezafibrate, on the oxygen dissociation curve of dilute hemoglobin solutions indicates a 4:1 binding stoichiometry with a site binding constant of 434 mol-1 for deoxyhemoglobin. Analysis of the combined effects of a range of bezafibrate and 2,3-diphosphoglycerate (DPG) concentrations indicates that 2 of the 4 bezafibrate sites are in the vicinity of the DPG binding site, and competitive with DPG binding, and 2 of the sites are remote from the DPG binding site.

Reduction in potency and reversal of left-shifting activity of BW12C with the major and minor components of chicken hemoglobin.

The effects of the left-shifting, anti-sickling compound BW12C (5-(2-formyl-3-hydroxyphenoxy)pentanoic acid) on the oxygen saturation curve of whole chicken blood and the isolated major (AII) and minor (AI) components of chicken hemoglobin have been studied. The results support the postulated major binding mode for BW12C to human hemoglobin of bridging between the alpha-chain terminal amino groups in the oxy conformation with an important hydrophobic component contributed mainly by Pro 77 alpha residues. In chicken AII (Pro 77 alpha----Ser) BW12C still left-shifts at high concentrations but its potency is greatly reduced (at least 10-fold). In chicken AI (Pro 77 alpha----Ser and Val 1 alpha----Met) BW12C is a right-shifter with a potency comparable to that of 2,3-diphosphoglycerate suggesting that binding at the beta-chain termini in the deoxy conformation is now dominant with alpha-chain binding no longer significant.

Skeletal blood flow in metabolic disorders of the skeleton.

Results are presented of measurements of skeletal blood flow made in 80 patients with painful benign or malignant diseases of the skeleton, excluding patients with Paget's disease. In crush fracture osteoporosis, total bone blood flow was slightly lower than normal although skeletal perfusion was normal. High values of bone blood flow were seen in 14/20 patients with osteomalacia and 3/12 patients with primary hyperparathyroidism. Very high values, comparable to those seen in the most severely affected patients with Paget's disease, were seen in polyostotic fibrous dysplasia, 2 out of 4 cases of Engelmann's disease and 1 out of 3 cases of renal osteodystrophy. Results were less elevated in myositis ossificans, secondary skeletal involvement with breast and prostatic carcinomata, myelomatosis and sympathetic osteodystrophy.